<<< Full experiment listing

PXD030820

PXD030820 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe Inhibitory Receptor Siglec-8 Interacts with FcεRI and Globally Inhibits Intracellular Signaling in Primary Mast Cells Upon Activation
DescriptionImmunomodulation of mast cell (MC) activity is warranted in allergic and inflammatory diseases where MCs have a central role in pathogenesis. Targeting Siglec-8, an inhibitory receptor on MCs and eosinophils, has shown promising activity in preclinical and clinical studies. While the intracellular pathways that regulate Siglec-8 activity in eosinophils have been well studied, the signaling mechanisms that lead to MC inhibition have not been fully elucidated. Here, we evaluate the intracellular signaling pathways of Siglec‐8‐mediated inhibition in primary MCs using an anti‐Siglec‐8 monoclonal antibody (mAb). Phospho‐proteomic profiling of FcεRI‐activated MCs revealed Siglec-8 mAb-treatment globally inhibited proximal and downstream kinases, leading to attenuated MC activation and degranulation. In fact, Siglec‐8 was found to directly interact with FcεRI signaling molecules. Siglec‐8 inhibition was dependent on both cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that interact with the SH2 containing protein phosphatase Shp-2 upon Siglec-8 phosphorylation. Taken together, these data support a model in which Siglec-8 regulates proximal FcεRI‐induced phosphorylation events through phosphatase recruitment and interaction with FcεRI, resulting in global inhibition of MCs upon Siglec-8 mAb engagement.
HostingRepositoryPRIDE
AnnounceDate2022-01-25
AnnouncementXMLSubmission_2022-01-25_05:23:58.465.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGian Luca Negri
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-01-07 12:50:19ID requested
12022-01-25 05:23:58announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Siglec-8, mast cell
Contact List
Brad Youngblood
contact affiliationAllakos Inc.
contact emailbyoungblood@allakos.com
lab head
Gian Luca Negri
contact affiliationIndependent researcher
contact emailnegri.gl@gmail.com
dataset submitter
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/01/PXD030820
PRIDE project URI
Repository Record List
[ + ]